Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Biomedical Engineering, Polytechnic University of Puerto Rico, San Juan, PR, USA.
Stem Cell Reports. 2023 Apr 11;18(4):999-1014. doi: 10.1016/j.stemcr.2023.03.001. Epub 2023 Mar 30.
Intramuscular fatty infiltration in muscle injuries and diseases, caused by aberrant adipogenesis of fibro-adipogenic progenitors, negatively impacts function. Intramuscular delivery of wingless-type MMTV integration site family 7a (WNT7A) offers a promising strategy to stimulate muscle regeneration, but its effects on adipogenic conversion of fibro-adipogenic progenitors remain unknown. Here, we show that WNT7A decreases adipogenesis of fibro-adipogenic progenitors (FAPs) by inducing nuclear localization of Yes-associated protein (YAP) through Rho in a β-CATENIN-independent manner and by promoting nuclear retention of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in differentiating FAPs. Furthermore, intramuscular injection of WNT7A in vivo effectively suppresses fatty infiltration in mice following glycerol-induced injury. Our results collectively suggest WNT7A as a potential protein-based therapeutic for diminishing adipogenesis of FAPs and intramuscular fatty infiltration in pathological muscle injuries or diseases.
肌内脂肪浸润在肌肉损伤和疾病中，由纤维脂肪祖细胞的异常脂肪生成引起，会对功能产生负面影响。Wnt 型 MMV 整合位点家族 7a（WNT7A）的肌内递送提供了一种有前途的刺激肌肉再生的策略，但它对纤维脂肪祖细胞的脂肪生成转化的影响尚不清楚。在这里，我们表明 WNT7A 通过 Rho 以 β-连环蛋白非依赖性方式诱导 Yes 相关蛋白 (YAP) 的核定位，并通过促进分化的 FAP 中 YAP 和 PDZ 结合基序转录共激活物 (TAZ) 的核保留，从而减少纤维脂肪祖细胞 (FAP) 的脂肪生成。此外，WNT7A 的体内肌内注射可有效抑制甘油诱导损伤后小鼠的脂肪浸润。我们的研究结果表明，WNT7A 作为一种潜在的蛋白治疗方法，可减少 FAP 的脂肪生成和病理性肌肉损伤或疾病中的肌内脂肪浸润。
Zotero 插件
